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1. CD4+ T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa

Author

Geng, Elvin H, Neilands, Torsten B, Thièbaut, Rodolphe, Bwana, Mwebesa Bosco, Nash, Denis, Moore, Richard D, Wood, Robin, Zannou, Djimon Marcel, Althoff, Keri N, Lim, Poh Lian, Nachega, Jean B, Easterbrook, Philippa J, Kambugu, Andrew, Little, Francesca, Nakigozi, Gertrude, Nakanjako, Damalie, Kiggundu, Valerian, Li, Patrick Chung Ki, Bangsberg, David R, Fox, Matthew P, Prozesky, Hans W, Hunt, Peter W, Davies, Mary-Ann, Reynolds, Steven J, Egger, Matthias, Yiannoutsos, Constantin T, Vittinghoff, Eric V, Deeks, Steven G, and Martin, Jeffrey N

Subjects
Epidemiology, Public Health, Health Sciences, Statistics, Mathematical Sciences, Sexually Transmitted Infections, Infectious Diseases, Genetics, HIV/AIDS, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Infection, Good Health and Well Being, Adult, Africa, Alkynes, Anti-HIV Agents, Asia, Benzoxazines, CD4 Lymphocyte Count, Cyclopropanes, Drug Therapy, Combination, Female, HIV Infections, Humans, Male, Nevirapine, North America, RNA, Viral, Virus Replication, HIV, antiretroviral therapy, CD4+T cell counts, immunological activation, Public Health and Health Services, Public health
Abstract

Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level < 500/μl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/μl was 529/μl [95% confidence interval (CI): 517-541] in North America, 494/μl (95% CI: 429-559) in West Africa, 515/μl (95% CI: 508-522) in Southern Africa, 503/μl (95% CI: 478-528) in Asia and 437/μl (95% CI: 425-449) in East Africa. Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.

Published
2015

2. CD4+ T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa

Author

Geng, Elvin H., Neilands, Torsten B., Thièbaut, Rodolphe, Bosco Bwana, Mwebesa, Nash, Denis, Moore, Richard D., Wood, Robin, Marcel Zannou, Djimon, Althoff, Keri N., Lian Lim, Poh, Nachega, Jean B., Easterbrook, Philippa J., Kambugu, Andrew, Little, Francesca, Nakigozi, Gertrude, Nakanjako, Damalie, Kiggundu, Valerian, Chung Ki Li, Patrick, Bangsberg, David R., Fox, Matthew P., Prozesky, Hans W., Hunt, Peter W., Davies, Mary-Ann, Reynolds, Steven J., Egger, Matthias, Yiannoutsos, Constantin T., Vittinghoff, Eric V., Deeks, Steven G., Martin, Jeffrey N., Geng, Elvin H., Neilands, Torsten B., Thièbaut, Rodolphe, Bosco Bwana, Mwebesa, Nash, Denis, Moore, Richard D., Wood, Robin, Marcel Zannou, Djimon, Althoff, Keri N., Lian Lim, Poh, Nachega, Jean B., Easterbrook, Philippa J., Kambugu, Andrew, Little, Francesca, Nakigozi, Gertrude, Nakanjako, Damalie, Kiggundu, Valerian, Chung Ki Li, Patrick, Bangsberg, David R., Fox, Matthew P., Prozesky, Hans W., Hunt, Peter W., Davies, Mary-Ann, Reynolds, Steven J., Egger, Matthias, Yiannoutsos, Constantin T., Vittinghoff, Eric V., Deeks, Steven G., and Martin, Jeffrey N.

Abstract

Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitor-based regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/µl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/µl was 529/µl [95% confidence interval (CI): 517-541] in North America, 494/µl (95% CI: 429-559) in West Africa, 515/µl (95% CI: 508-522) in Southern Africa, 503/µl (95% CI: 478-528) in Asia and 437/µl (95% CI: 425-449) in East Africa. Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level

Published
2017

3. CD4+ T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa

Author

Geng, Elvin H., Neilands, Torsten B., Thièbaut, Rodolphe, Bosco Bwana, Mwebesa, Nash, Denis, Moore, Richard D., Wood, Robin, Marcel Zannou, Djimon, Althoff, Keri N., Lian Lim, Poh, Nachega, Jean B., Easterbrook, Philippa J., Kambugu, Andrew, Little, Francesca, Nakigozi, Gertrude, Nakanjako, Damalie, Kiggundu, Valerian, Chung Ki Li, Patrick, Bangsberg, David R., Fox, Matthew P., Prozesky, Hans W., Hunt, Peter W., Davies, Mary-Ann, Reynolds, Steven J., Egger, Matthias, Yiannoutsos, Constantin T., Vittinghoff, Eric V., Deeks, Steven G., and Martin, Jeffrey N.

Subjects
Adult, Cyclopropanes, Male, Asia, Anti-HIV Agents, Epidemiology, antiretroviral therapy, HIV Infections, Virus Replication, CD4+T cell counts, Drug Therapy, Clinical Research, Genetics, Humans, Nevirapine, Viral, immunological activation, Statistics, Evaluation of treatments and therapeutic interventions, HIV, Benzoxazines, CD4 Lymphocyte Count, Infectious Diseases, Good Health and Well Being, 6.1 Pharmaceuticals, Alkynes, Africa, Combination, North America, Public Health and Health Services, HIV/AIDS, RNA, Female, Infection
Abstract

Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level < 500/μl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/μl was 529/μl [95% confidence interval (CI): 517-541] in North America, 494/μl (95% CI: 429-559) in West Africa, 515/μl (95% CI: 508-522) in Southern Africa, 503/μl (95% CI: 478-528) in Asia and 437/μl (95% CI: 425-449) in East Africa. Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.

Published
2015

4. CD41 T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa

Author

Geng, Elvin H, Neilands, Torsten B, Thièbaut, Rodolphe, Bwana, Mwebesa Bosco, Nash, Denis, Moore, Richard D, Wood, Robin, Zannou, Djimon Marcel, Althoff, Keri N, Lim, Poh Lian, Nachega, Jean B, Easterbrook, Philippa J, Kambugu, Andrew, Little, Francesca, Nakigozi, Gertrude, Nakanjako, Damalie, Kiggundu, Valerian, Ki Li, Patrick Chung, Bangsberg, David R, Fox, Matthew P, Prozesky, HansW, Hunt, Peter W, Davies, Mary-Ann, Reynolds, Steven J, Egger, Matthias, Yiannoutsos, Constantin T, Vittinghoff, Eric V, Deeks, Steven G, and Martin, Jeffrey N

Subjects
610 Medicine & health, 360 Social problems & social services, 3. Good health
Abstract

BACKGROUND Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. METHODS We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level

5. CD4+ T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa

Author

Geng, Elvin H., Neilands, Torsten B., Thièbaut, Rodolphe, Bosco Bwana, Mwebesa, Nash, Denis, Moore, Richard D., Wood, Robin, Marcel Zannou, Djimon, Althoff, Keri N., Lian Lim, Poh, Nachega, Jean B., Easterbrook, Philippa J., Kambugu, Andrew, Little, Francesca, Nakigozi, Gertrude, Nakanjako, Damalie, Kiggundu, Valerian, Chung Ki Li, Patrick, Bangsberg, David R., Fox, Matthew P., Prozesky, Hans W., Hunt, Peter W., Davies, Mary-Ann, Reynolds, Steven J., Egger, Matthias, Yiannoutsos, Constantin T., Vittinghoff, Eric V., Deeks, Steven G., Martin, Jeffrey N., Geng, Elvin H., Neilands, Torsten B., Thièbaut, Rodolphe, Bosco Bwana, Mwebesa, Nash, Denis, Moore, Richard D., Wood, Robin, Marcel Zannou, Djimon, Althoff, Keri N., Lian Lim, Poh, Nachega, Jean B., Easterbrook, Philippa J., Kambugu, Andrew, Little, Francesca, Nakigozi, Gertrude, Nakanjako, Damalie, Kiggundu, Valerian, Chung Ki Li, Patrick, Bangsberg, David R., Fox, Matthew P., Prozesky, Hans W., Hunt, Peter W., Davies, Mary-Ann, Reynolds, Steven J., Egger, Matthias, Yiannoutsos, Constantin T., Vittinghoff, Eric V., Deeks, Steven G., and Martin, Jeffrey N.

Abstract

Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitor-based regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/µl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/µl was 529/µl [95% confidence interval (CI): 517-541] in North America, 494/µl (95% CI: 429-559) in West Africa, 515/µl (95% CI: 508-522) in Southern Africa, 503/µl (95% CI: 478-528) in Asia and 437/µl (95% CI: 425-449) in East Africa. Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level

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